Major Areas of Research
- Studies of the mechanisms by which antimicrobial resistance emerges in the natural context of human infection
- Genomic sequencing of historical clinical bacterial isolates to characterize evolutionary pathways by which present day resistance to specific antimicrobial drug classes has evolved
- Genomic and proteomic approaches to study gene expression and transcriptional control mechanisms in resistance plasmids
- Development of novel genomic and proteomic assays for rapid resistance diagnostics in the clinical microbiology laboratory
- Study of the pathogenesis of bacterial infections in patients with primary immunodeficiency diseases
- Application of population genomics approaches to study in vivo adaptive evolution of bacterial infections in the context of acute or chronic infection
The emergence and spread of antimicrobial resistance (AMR) in bacteria has been recognized as a critical threat to public health. Many important classes of bacterial AMR undergo selection and evolution in the natural context of antibiotic treatment in a human host, though important features of host context are not commonly included in studies of AMR. One of the main areas of focus within the Bacterial Pathogenesis and Antimicrobial Resistance Unit is the application of genomic techniques to understand the evolutionary mechanisms by which resistance emerges in this natural context. The approaches applied include sequencing of current and historical clinical bacterial isolates in combination with in vitro models of adaptive evolution to characterize pathways by which present day resistance to specific antimicrobial drug classes has evolved. As many of the clinically important resistance genes are located within bacterial plasmids, the laboratory is also focused on the study of principles of plasmid evolution and mechanisms controlling gene expression in resistance plasmids. RNA-seq and proteomics approaches are applied to these problems.
Another important area of focus within the unit is the study of bacterial pathoadaptation in the immunocompromised host. Population genomics approaches are applied in combination with molecular genetic analysis to understand selection dynamics and host-pathogen interactions in the context of defined genetic immunodeficiency diseases.
Recent progress in characterizing molecular mechanisms of antimicrobial resistance has also made possible the development of new approaches to the detection of AMR based on proteomics and sequencing. The Bacterial Pathogenesis and Antimicrobial Resistance Unit has developed novel approaches to rapid AMR diagnostics based on mass spectrometry and nanopore sequencing, and work in this area is a key focus of the laboratory.
Dr. Dekker received his M.D. from Harvard Medical School and Ph.D. from Harvard University through the NIH Medical Scientist Training Program. He completed pathology residency and fellowship training in medical microbiology at Massachusetts General Hospital and is board-certified in clinical pathology and medical microbiology through the American Board of Pathology. In 2013, he joined the NIH Clinical Center as a senior staff member of the Microbiology Service in the Department of Laboratory Medicine. In this role, he co-directed the Bacteriology, Specimen Processing, Parasitology, and Molecular Epidemiology sections of the laboratory before serving as acting chief of the Microbiology Service in 2018. In 2018, Dr. Dekker was named as a Lasker Clinical Research Scholar and recruited as a tenure-track investigator within the NIAID intramural research program, where he established the Bacterial Pathogenesis and Antimicrobial Resistance Unit within the Laboratory for Clinical Immunology and Microbiology. In addition, he continues to oversee the Genomics Section within the Microbiology Service, which focuses on development of next-generation sequencing-based approaches with applications in epidemiology and infectious diseases.
Dr. Dekker serves on the Clinical Center Hospital Infection Control Committee and the NIAID Infectious Disease Fellowship Committee. He served on FDA Anti-Infective Drug Advisory Committees in 2013 and 2014. He is also a member of the editorial board for Journal of Clinical Microbiology. In 2016, Dr. Dekker received the Beckman-Coulter Young Investigator award from the American Society for Microbiology, and he received an NIH Clinical Center CEO Award in 2017 for developing diagnostic methods using next-generation sequencing for improved rapid infectious disease and antibiotic resistance diagnosis.
Pavel Khil, Ph.D.
Augusto Dulanto Chiang, M.D.
Adrien Launay, Ph.D.
Andrew Clark, Ph.D.
Information for Prospective Laboratory Trainees
If you wish to inquire about postdoctoral or other positions in the Bacterial Pathogenesis and Antimicrobial Resistance Unit, contact Dr. Dekker.
Lemon JK, Khil PP, Frank KM, Dekker JP. Rapid nanopore sequencing of plasmids and resistance gene detection in clinical isolates. J Clin Microbiol. 2017 Dec;55(12):3530-3543.
Wang H, Drake SK, Youn, JH, Rosenberg, AZ, Yong C, Gucek M, Suffredini AF, Dekker JP. Peptide markers for rapid detection of KPC carbapenemase by LC-MS/MS. Sci Rep. 2017 May 31;7(1):2531.
Wang H, Drake SK, Yong C, Gucek M, Tropea M, Lyes M, Rosenberg AZ, Soderblom E, Mayer-Salmon M, Arthur Moseley M, Dekker JP, and Suffredini AF. A genoproteomic approach to detect peptide markers of bacterial respiratory pathogens. Clin Chem. 2017 Aug;63(8):1398-1408.
Dekker JP. Molecular assay validation using genomic sequence databases. J Clin Microbiol. 2016 Dec;54(12):2854-2856.
He S, Hickman AB, Varani AM, Siguier P, Chandler M, Dekker JP, Dyda F. Insertion sequence IS26 reorganizes plasmids in clinically isolated multidrug-resistant bacteria by replicative transposition. MBio. 2015 Jun 9;6(3):e00762.
Lau AF, Wang H, Weingarten RA, Drake SK, Suffredini AF, Garfield MK, Chen Y, Gucek M, Youn JH, Stock F, Tso H, DeLeo J, Cimino JJ, Frank KM, Dekker JP. A rapid matrix-assisted laser desorption ionization-time of flight mass spectrometry-based method for single-plasmid tracking in an outbreak of carbapenem-resistant Enterobacteriaceae. J Clin Microbiol. 2014 Aug;52(8):2804-12.